Objectives and Research Aims: Neurogenic bladder resulting from disorders such as spinal cord injury (SCI) can have a devastating impact on patients and their families, resulting in a high cost to the individual and to society. The long-term goal of this research program is to develop neural prostheses to chronically restore urinary continence in persons with SCI. Neurogenic bladder can result in reflex bladder activity that can result in urinary incontinence, renal damage and autonomic dysreflexia. Research Design and Methods: This study proposes using chronic electrical stimulation of the genital nerve (GN) to produce a decrease in upper motor neuron bladder sequelae in persons with SCI. Acute electrical stimulation of the GN in persons with incomplete SCI will also be conducted to determine tolerance and effectiveness in this previously unstudied human population subset. Electrical stimulation of the GN provides an immediate, reversible approach to electrically shutting down unwanted upper motor neuron neurogenic bladder sequelae. We have demonstrated in animal models and one chronic human model that this approach reduces the target reflexes and has potential to restore continence. Specifically, we will determine chronic safety and efficacy of this approach in humans to produce urinary continence in SCI. Surface electrodes will be placed on the shaft of the penis to stimulate the GN, and urodynamic studies will be conducted every two weeks over the course of the ten week study to obtain estimates of bladder capacity. Stimulus parameters for effective GN stimulation will be obtained at the urodynamic study (UDS) prior to stimulation initiation in chronic testing subjects, or at the single urodynamic study conducted for subjects with incomplete SCI. The effectiveness of stimulation will be determined based upon the increase in bladder capacity in all subjects during UDS. Chronic testing will measure the clinical and bladder pressure impact of the chronic stimulation. In persons who intermittently catheterize, stimulation is anticipated to decrease the number and severity of incontinent episodes, as well as increased fluid intake and decreased catheterization frequency; fluid and catheterization frequency changes common temporizing measures utilized to decrease urinary incontinence in SCI. In persons with indwelling catheters it is expected to reduce the number and intensity of bladder spasms as well as average bladder pressures in persons with indwelling catheters. CLINICAL SIGNIFICANCE: Successful completion of this collaborative project between basic scientists and physicians will demonstrate the efficacy of producing chronic continence via electrical stimulation of peripheral afferent nerves. This has immediate clinical potential and wil provide justification for initiating work aimed at producing clinical trials for a non-invasive devce. In addition to non-invasive surface stimulation for bladder continence, these results can be translated into a chronically implanted medical device. A long term goal of this research is to develop an implanted stimulator, connected by a lead to an electrode placed near the corresponding afferent nerve. The Cleveland FES Center has the technology and expertise to develop the implanted device. Future projects will develop the implanted system, including validation using percutaneous electrodes placed near the anatomical targets identified in this study. The information obtained from this project will lay the groundwork for developing and testing an implanted system, leading to the first implants during the next project and generating data to support FDA approval and clinical trials. PUBLIC HEALTH RELEVANCE: Although about 11% of Americans are veterans, 25% of all individuals with spinal cord injuries (SCIs) in the US are veterans. Neurogenic bladder is a common neurologic complication associated with SCI. In addition to being a debilitating and costly condition, neurogenic bladder compromises the ability to be productive in the workplace, engage in social or leisure activities, pursue an education, and participate in other activities associated with an independent and productive lifestyle. Neurogenic bladder frequently leads to other urologic complications, such as incontinence, urinary tract infection, renal damage and consequent renal dialysis or transplantation which can lead to recurrent and costly hospitalization. This project directly addresses the problem of neurogenic bladder by providing a means to reduce bladder over-activity. This approach is less invasive than existing devices and is expected to expand the population of individuals able to benefit from neural stimulation systems to restore bladder function.